Identification of cell-specific soluble mediators and cellular targets during cell therapy for the treatment of heart failure.
Cell therapy, the transplantation of progenitor cells into the myocardium, has been proposed as a possible treatment strategy for heart failure. Despite the lack of repopulation of the heart with progenitor cells, cell therapy induces a modest but well-documented functional improvement in patients. It is thought that paracrine mechanisms may account for the observed changes in heart function. However, there is little evidence that directly supports this hypothesis. We discuss the current views in the literature and present some preliminary data proposing that adult progenitor cells influence contractility and Ca2+ handling in neighboring failing cardiomyocytes by soluble mediators. This can be tested using a co-culture system. Our results suggest that soluble mediators from adult progenitor cells can enhance failing cardiomyocyte function, supporting the paracrine hypothesis. This co-culture strategy can be employed to identify cell-specific soluble mediators and their cellular targets during cell therapy for the treatment of heart disease.
Lee
Joon
J
Laboratory of Cell Electrophysiology, Heart Science Centre, Harefield Hospital, Hill End Road, Harefield, Middlesex UB96JH, UK.
Stagg
Mark A
MA
Siedlecka
Urszula
U
Latif
Najma
N
Soppa
Gopal Kr
GK
Yacoub
Magdi
M
Terracciano
Cesare Mn
CM
D053687:Adult Stem Cells / Q000166:cytology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D064987:Cell- and Tissue-Based Therapy; D018920:Coculture Techniques; D005260:Female; D006333:Heart Failure / Q000628:therapy*; D006801:Humans; D032383:Myocytes, Cardiac / Q000473:pathology; D009928:Organ Specificity; D019899:Paracrine Communication; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
D002118:Calcium